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No association between cyclooxygenase-2 and uridine diphosphate glucuronosyltransferase 1A6 genetic polymorphisms and colon cancer risk

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World journal of Gastroenterology 2009年第18期15卷 2240-2244页

作者： Cheryl L Thompson sarah j Plummer Alona Merkulova Iona Cheng Thomas C Tucker Graham Casey Li Li Departments of Family Medicine and Epidemiology and Biostatistics Case Centerfor Transdisciplinary Research on Energetics and CancerCase Comprehensive Cancer Center Case Western Reserve University. Cleveland OH 44106-7136 United States Department of Preventive Medicine University of Southern California Los Angeles CA90033-1006 United States Department of Cancer Biology Cleveland Clinic Foundation Cleveland OH 44195-0001 United States Department of Epidemiology and Biostatisticsand Institute for Human Genetics University of California SanFrancisco San Francisco CA 94143-0644 United States Markey Cancer Center University of Kentucky Lexington KY 40504-3381 United States

AIM：To investigate the association of variations in the cyclooxygenase-2 （COX2） and uridine diphosphate glucuronosyltransferase 1A6 （UGTIA6） genes and non-steroidal anti-inflammatory drugs （NSAIDs） use with risk of colon ***： NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGTIA6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms （SNPs） in the COX2 and UGTIA6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population ***： No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk （P 〉 0.05）,and we did not observe that these variants modify the protective effect of NSAIDs （P 〉 0.05）. We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon ***： Our study does not support a role of COX2 and UGTIA6 genetic variations in the development of colon cancer.

关键词： Uridine diphosphate glucuronosyltransferase 1A6 Cyclooxygenase-2 Non-steroidal anti-inflammatorydrugs Colon cancer Genetic association studies Singlenucleotide polymorphisms

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Persistent diarrhea with petechial rash-unusual pattern of light chain amyloidosis deposition on skin and gastrointestinal biopsies:A case report

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World journal of Clinical Cases 2022年第28期10卷 10252-10259页

作者： Shawna E Bilton Nikhil Shah Diana Dougherty sarah Simpson Alex Holliday Farhad Sahebjam Douglas j Grider Department of Basic Science Education Virginia Tech Carilion School of MedicineRoanokeVA 24016United States Department of Internal Medicine Carilion ClinicRoanokeVA 24016United States Gastroenterology and Hepatology Section Department of Internal MedicineCarilion ClinicRoanokeVA 24016United States Dermatology Section Department of Internal MedicineCarilion ClinicRoanokeVA 24016United States Dominion Pathology Associates RoanokeVA 24018United States

BACKGROUND Amyloidosis is a rare disease characterized by extracellular deposition of misfolded protein aggregated into insoluble *** involvement in systemic amyloidosis is common,but is often subclinical or presents as vague and nonspecific *** is rare for gastrointestinal symptoms to be the main presenting symptom in patients with systemic amyloidosis,causing it to be undiagnosed until late-stage *** SUMMARY A 53 year-old man with diarrhea,hematochezia,and weight loss presented to a community *** with biopsy at that time was suspicious for Crohn *** to worsening symptoms including nausea,vomiting,and a new petechial rash,an abdominal fat pad biopsy was *** biopsy showed papillary and adnexal dermal amyloid deposition,in a pattern usually seen with cutaneous ***,Cytokeratin 5/6 was negative,excluding cutaneous *** patterns of nodular amyloidosis,subcutaneous amyloid deposits and perivascular amyloid were not *** Acid-Schiff stain was negative for lipoid proteinosis,Congo red was positive for apple green birefringence on polarization and amyloid typing confirmed amyloid light chain *** endoscopic biopsies of the gastrointestinal tract showed amyloid deposition from the esophagus to the rectum,in a pattern usually seen in serum amyloid A in the setting of chronic inflammatory diseases,including severe inflammatory bowel *** marrow biopsy showed kappa-restricted plasma cell *** Described is an unusual presentation of primary systemic amyloidosis,highlighting the risk of misdiagnosis with subsequent significant organ dysfunction and high mortality.

关键词： Light chain amyloidosis Diarrhea Endoscopy Petechial rash Plasma cell dyscrasia Case report

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Long term follow-up of a family with GUCY2D dominant cone dystrophy

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International journal of Ophthalmology(English edition) 2018年第12期11卷 1945-1950页

作者： Georgios Tsokolas Hussein Almuhtaseb Helen Griffiths Fatima Shawkat Reuben j.Pengelly sarah Ennis Andrew Lotery Clinical and Experimental Sciences University of Southampton Eye Unit University Hospital Southampton Human Genetics & Genomic Medicine Faculty of Medicine University of Southampton

AIM: To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. METHODS: Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms(ERGs) and occipital pattern reversal visual evoked potentials were recorded. RESULTS: Two members of the same family(father and son) were identified to have the heterozygous R838 C mutation in the GUCY2D gene. The father presented at the age of 45 with bilateral bull’s eye maculopathy and temporal disc pallor. Over 13 y of serial follow up visits, the bull’s eye maculopathy progressed gradually into macular atrophy. Electrophysiological tests were significantly degraded suggesting poor macular function. Spectraldomain optical coherence tomography(SD-OCT) scans showed progressive loss and disruption of the ellipsoid layer at the foveal level. His son presented at the age of 16 with bilateral granular retinal pigment epithelial changes in both maculae. Electrophysiological testing was initially borderline normal but has gradually deteriorated to show reduced cone ERGs and macula function. SD-OCT demonstrated gradual macular thinning and atrophy bilaterally. Unlike his father, there was no disruption of the ellipsoid ***: Both family members exhibited gradual changes in their fundi, electrophysiological testing and multimodal imaging. Changes were milder than those observed in other mutations of the same gene.

关键词： autofluorescence electroretinogram cone dystrophy cone-rod dystrophy GUCY2D spectral-domain optical coherence tomography visual evoked potential

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Helicobacter pylori eradication therapy for functional dyspepsia: Systematic review and meta-analysis

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World journal of Gastroenterology 2016年第12期22卷 3486-3495页

作者： Li-jun Du Bin-Rui Chen john j Kim sarah Kim jin-Hua Shen Ning Dai Department of Gastroenterology Sir Run Run Shaw Hospital Zhejiang University Hangzhou 310020 Zhejiang Province China Division of Gastroenterology Loma Linda University Loma Linda CA 92354 United States

AIM: To evaluate whether Helicobacter pylori (H. pylori) eradication therapy benefits patients with functional dyspepsia (FD).METHODS: Randomized controlled trials (RCTs) investigating the efficacy and safety of H. pylori eradication therapy for patients with functional dyspepsia published in English (up to May 2015) were identified by searching PubMed, EMBASE, and The Cochrane Library. Pooled estimates were measured using the fixed or random effect model. Overall effect was expressed as a pooled risk ratio (RR) or a standard mean difference (SMD). All data were analyzed with Review Manager 5.3 and Stata ***: This systematic review included 25 RCTs with a total of 5555 patients with FD. Twenty-three of these studies were used to evaluate the benefits of H. pylori eradication therapy for symptom improvement; the pooled RR was 1.23 (95%CI: 1.12-1.36, P < 0.0001). H. pylori eradication therapy demonstrated symptom improvement during long-term follow-up at ≥ 1 year (RR = 1.24; 95%CI: 1.12-1.37, P < 0.0001) but not during short-term follow-up at < 1 year (RR = 1.26; 95%CI: 0.83-1.92, P = 0.27). Seven studies showed no benefit of H. pylori eradication therapy on quality of life with an SMD of -0.01 (95%CI: -0.11 to 0.08, P = 0.80). Six studies demonstrated that H. pylori eradication therapy reduced the development of peptic ulcer disease compared to no eradication therapy (RR = 0.35; 95%CI: 0.18-0.68, P = 0.002). Eight studies showed that H. pylori eradication therapy increased the likelihood of treatment-related side effects compared to no eradication therapy (RR = 2.02; 95%CI: 1.12-3.65, P = 0.02). Ten studies demonstrated that patients who received H. pylori eradication therapy were more likely to obtain histologic resolution of chronic gastritis compared to those who did not receive eradication therapy (RR = 7.13; 95%CI: 3.68-13.81, P < 0.00001).CONCLUSION: The decision to eradicate H. pylori in patients with functional

关键词： Functional dyspepsia Helicobacter pylori eradication Symptom improvement Quality of life Peptic ulceration Meta-analysis

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Robust Voice Activity Detection using Cepstral Features

Robust Voice Activity Detection using Cepstral Features

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计算机，通信，控制与电力工程国际会议

作者： j. A. haigh j. S. Mason Speech Research Group Electrical Engineering Department University College Swansea SWANSEASA2 8PPUK

This paper reviews algorithms which rely on the analysis of time domain samples to provide energy and zero-crossing rates,together with more recent algorithms that use different methods for speech *** then examine a different,approach using cepstral analysis,showing a high degree of amplitude and noise level independence. We show that a cepstral based algorithm exhibits a high degree of independence to levels of background noise and successful speech end-pointing can be achieved via thresholding cepstral distance *** the use of a noise code-book we are able to provide a successful reference for Euclidean distance measures in the voice detection algorithm.

关键词： VAD Robust Voice Activity Detection using Cepstral Features Activity

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Characterizing the Relative Importance Assigned to Physical Variables by Climate Scientists when Assessing Atmospheric Climate Model Fidelity

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Advances in Atmospheric Sciences 2018年第9期35卷 1101-1113页

作者： Susannah M.BURROWS Aritra DASGUPTA sarah REEHL Lisa BRAMER Po-Lun MA Philip j.RASCH Yun QIAN Pacific Northwest National Laboratory RichlandWashington 99354USA

Evaluating a climate model＇s fidelity（ability to simulate observed climate） is a critical step in establishing confidence in the model＇s suitability for future climate projections, and in tuning climate model parameters. Model developers use their judgement in determining which trade-offs between different aspects of model fidelity are acceptable. However, little is known about the degree of consensus in these evaluations, and whether experts use the same criteria when different scientific objectives are defined. Here, we report on results from a broad community survey studying expert assessments of the relative importance of different output variables when evaluating a global atmospheric model＇s mean climate. We find that experts adjust their ratings of variable importance in response to the scientific objective, for instance, scientists rate surface wind stress as significantly more important for Southern Ocean climate than for the water cycle in the Asian watershed. There is greater consensus on the importance of certain variables（e.g., shortwave cloud forcing） than others（e.g., aerosol optical depth）. We find few differences in expert consensus between respondents with greater or less climate modeling experience,and no statistically significant differences between the responses of climate model developers and users. The concise variable lists and community ratings reported here provide baseline descriptive data on current expert understanding of certain aspects of model evaluation, and can serve as a starting point for further investigation, as well as developing more sophisticated evaluation and scoring criteria with respect to specific scientific objectives.

关键词： climate climate model model evaluation numerical model skill expert elicitation

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Emerging roles of circular RNAs in retinal diseases

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Neural Regeneration Research 2022年第9期17卷 1875-1880页

作者： Aneliya Hanineva Karen Sophia Park joshua j.Wang Margaret M.DeAngelis Michael H.Farkas sarah X.Zhang Department of Ophthalmology and Ross Eye Institute Jacobs School of Medicine and Biomedical SciencesUniversity at BuffaloState University of New YorkBuffaloNYUSA Research Service Veterans Administration Western New York Healthcare SystemBuffaloNYUSA Department of Biochemistry Jacobs School of Medicine and Biomedical SciencesUniversity at BuffaloState University of New YorkBuffaloNYUSA

Retinal disorders are a group of ocular diseases whose onset is associated with a number of aberrant molecular and cellular processes or physical damages that affect retinal structure and function resulting in neural and vascular degeneration in the *** research has primarily focused on delaying retinal disease with minimal success in preventing or reversing neuronal *** this review,we explore a relatively new field of research involving circular RNAs,whose potential roles as biomarkers and mediators of retinal disease pathogenesis have only just *** knowledge of circular RNAs function is limited given its novelty,current evidence has highlighted their roles as modulators of microRNAs,regulators of gene transcription,and biomarkers of disease development and ***,we summarize how circular RNAs may be implicated in the pathogenesis of common retinal diseases including diabetic retinopathy,glaucoma,proliferative vitreoretinopathy,and age-related macular ***,we explore the potential of circular RNAs as novel biomarkers and therapeutic targets for the diagnosis and treatment of retinal diseases.

关键词： age-related macular degeneration circular RNA diabetic retinopathy glaucoma microRNA proliferative vitreoretinopathy retina

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No association between phosphatase and tensin homolog genetic polymorphisms and colon cancer

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World journal of Gastroenterology 2009年第30期15卷 3771-3775页

作者： Lynette S Phillips Cheryl L Thompson Alona Merkulova sarah j Plummer Thomas C Tucker Graham Case Li Li Department of Epidemiology and Biostatistics and Case Comprehensive Cancer Center Case Western Reserve University Cleveland OH 44106-7136 United States Departments of Family Medicine and Epidemiology and Biostatistics Case Center for Transdisciplinary Research on Energetics and Cancer Case Comprehensive Cancer Center Case Western Reserve University Cleveland OH 44106-7136m United States Department of Cancer Biology Cleveland Clinic Foundation Cleveland OH 44195-0001 United States Graham Casey Department of Preventive Medicine University of Southern California Los Angeles CA 90033-1006 United States assisted with patient referrals recruitment and reviewed the manuscript coordinated the lab work and reviewed the manuscript Li L led the study design data collection and assisted with the manuscript preparation

AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homolog (PTEN) tumor suppressor gene and risk of colon cancer. METHODS: We utilized a population-based casecontrol study of incident colon cancer individuals (n= 421) and controls (n = 483) aged ≥ 30 years to conduct a comprehensive tagSNP association analysis of the PTEN gene. RESULTS: None of the PTEN SNPs were statistically significantly associated with colon cancer when controlled for age, gender, and race, or when additionally adjusted for other known risk factors (P > 0.05). Haplotype analyses similarly showed no association between the PTEN gene and colon cancer. CONCLUSION: Our study does not support PTEN as a colon cancer susceptibility gene.

关键词： Colon cancer Phosphatase and tensinhomolog Candidate gene Genetic polymorphisms Single nucleotide polymorphism association

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Correlation of endoscopic disease severity with pediatric ulcerative colitis activity index score in children and young adults with ulcerative colitis

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World journal of Gastroenterology 2017年第18期23卷 3322-3329页

作者： Basavaraj Kerur Heather j Litman julia Bender Stern sarah Weber jenifer R Lightdale Paul A Rufo Athos Bousvaros Pediatric Gastroenterology Hasbro Children's Hospital Corrona LLC Southborough Inflammatory Bowel Disease Center Children's Hospital Boston Division of Pediatric Gastroenterology UMass Memorial Medical CenterUniversity Campus Worcester

To investigate of pediatric ulcerative colitis activity index (PUCAI) in ulcerative colitis correlate with mucosal inflammation and endoscopic assessment of disease activity (Mayo endoscopic score).METHODSWe reviewed charts from ulcerative colitis patients who had undergone both colonoscopy over 3 years. Clinical assessment of disease severity within 35 d (either before or after) the colonoscopy were included. Patients were excluded if they had significant therapeutic interventions (such as the start of corticosteroids or immunosuppressive agents) between the colonoscopy and the clinical assessment. Mayo endoscopic score of the rectum and sigmoid were done by two gastroenterologists. Inter-observer variability in Mayo score was *** identified 99 patients (53% female, 74% pancolitis) that met inclusion criteria. The indications for colonoscopy included ongoing disease activity (62%), consideration of medication change (10%), assessment of medication efficacy (14%), and cancer screening (14%). Based on PUCAI scores, 33% of patients were in remission, 39% had mild disease, 23% had moderate disease, and 4% had severe disease. There was “moderate-substantial” agreement between the two reviewers in assessing rectal Mayo scores (kappa = 0.54, 95%CI: 0.41-0.68).CONCLUSIONEndoscopic disease severity (Mayo score) assessed by reviewing photographs of pediatric colonoscopy has moderate inter-rater reliability, and agreement was less robust in assessing patients with mild disease activity. Endoscopic disease severity generally correlates with clinical disease severity as measured by PUCAI score. However, children with inflamed colons can have significant variation in their reported clinical symptoms. Thus, assessment of both clinical symptoms and endoscopic disease severity may be required in future clinical studies.

关键词： Ulcerative colitis Pediatric ulcerative colitis activity index Mayo score

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Hospital readmissions in decompensated cirrhotics: Factors pointing toward a prevention strategy

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World journal of Gastroenterology 2017年第37期23卷 6868-6876页

作者： Siamak M Seraj Emily j Campbell sarah K Argyropoulos Kara Wegermann Raymond T Chung james M Richter Massachusetts General Hospital Division of Gastroenterology Duke University Hospital Department of Medicine Harvard Medical School

AIM To reduce readmissions and improve patient outcomes in cirrhotic patients through better understanding of readmission *** We performed a single-center retrospective study of patients admitted with decompensated cirrhosis from january 1, 2011 to December 31, 2013(n = 222). Primary outcomes were time to first readmission and 30-d readmission rate due to complications of cirrhosis. Clinical and demographic data were collected to help describe predictors of readmission, along with care coordination measures such as post-discharge status and outpatient follow-up. Univariate and multivariateanalyses were performed to describe variables associated with *** One hundred thirty-two patients(59.4%) were readmitted at least once during the study period. Median time to first and second readmissions were 54 and 93 d, respectively. Thirty and 90-d readmission rates were 20.7 and 30.1 percent, respectively. Predictors of 30-d readmission included education level, hepatic encephalopathy at index, ALT more than upper normal limit and Medicare coverage. There were no statistically significant differences in readmission rates when stratified by discharge disposition, outpatient follow-up provider or time to first outpatient *** Readmissions are challenging aspect of care for cirrhotic patients and risk continues beyond 30 d. More initiatives are needed to develop enhanced, longitudinal post-discharge systems.

关键词： Chronic disease Re-hospitalizations Liver disease Readmissions Cirrhosis Chronic care

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